Wright
and colleagues found that cells expressing the p48 gene, blue hat-wearing cells, formed the pancreas. When the investigators knocked out the p48
gene, they found that cells, which would have normally formed the pancreas, became intestinal cells instead.

“The really important point is that
these cells without p48 don’t just die; they go on to behave as a different tissue,” Wright says. “That is very powerful information
when you are thinking about manipulating stem cells in the laboratory. Because you know now — at least for some genes — that you can put them in or
take them away and you don’t kill the cells; you manipulate what they’re going to become. And that’s exactly what we want to do
therapeutically.”

The next step, he says, is to see whether introducing the p48 gene into cells that would normally become intestinal
cells changes their fate and causes them to become pancreas cells instead.

“If we can do that,” Wright says, “we’re a big step
further towards knowing that p48 is one of the gene triggers that you might want to put into an embryonic or other stem cell to make
pancreas.”

But one of how many? Wright wonders. “We’re just sort of clutching and still trying to get some basic understanding.
It’s like climbing an ice wall with ice picks: you’d better have a good hold before you start going up too high.”

Even knowing the
complete set of factors that will convert stem cells into pancreas doesn’t address the logistical problems of applying that information on a large scale
to generate products for human transplantation. Simple manipulation of laboratory growth conditions, for example, may not be sufficiently rigorous to pass FDA
muster.

“We have to understand very deeply the physiological behavior of those cells,” Wright adds. “How long do we spend
characterizing those cell types before we say it’s appropriate to put them into people? I don’t know the answer to that.”

At the end
of the day, it is the fundamental academic question that drives Wright’s quest for answers. Relaxing in his office of frog companions, he ponders the
intricacies of pancreas development. “I’m still fascinated by how a piece of tissue buds out, goes through a branching process, makes the right
numbers of cells of different types, and generates an organ that works so beautifully,” he says. “It’s an amazing thing.”